Non-peptide inhibitors of HCV serine proteinase.
We screened a chemical library of 2000 compounds for inhibitors of hepatitis C virus (HCV) serine proteinase using an in vitro screening method measuring the hydrolysis of the peptide substrate. Three compounds were found to be the most potent inhibitors (IC50 < 10(-5) M). Two of them had a similar structure, that of halogenated benzanilide, and were not inhibitory for common serine proteinases. They inhibited the enzyme non-competitively with the substrate. Together with the result of the analogous compounds in the chemical library, the presumed structural requirements of the inhibition are pointed out.
Kakiuchi
N
N
HQL Research Laboratories, Sumitomo Metal Industries, Kyoto, Japan. nkakiuch@virus.kyoto-u.ac.jp
Komoda
Y
Y
Komoda
K
K
Takeshita
N
N
Okada
S
S
Tani
T
T
Shimotohno
K
K
D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D010455:Peptides; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus